A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained 3 release of antigen and has intrinsic pro-inflammatory and adjuvant activities which 4 are dependent on MyD88 adaptor protein

FERNANDA SÁNCHEZ-VALLECILLO; MARÍA MINGUITO DE LA ESCALERA; MARÍA VIRGINIA AGUIRRE; GABRIELA ULLIO; SANTIAGO PALMA; LETICIA GONZALEZ-CINTADO; ANA CHIODETTI; GERMAN SOLDANO; G MORON; DANIEL ALLEMANDI; CARLOS ARDAVÍN; MARÍA C PISTORESI- PALENCIA.; BELKYS A. MALETTO

JOURNAL OF CONTROLLED RELEASE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 vol. 214 p. 12 - 22

0168-3659

Modern subunitvaccines require the development of new adjuvant strategies. Recently, weshowed that CpG-ODN formulated with a liquid crystal nanostructure formed byself assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system forpromoting an antigen-specific immune response to weak antigens. Here, we showedthat after subcutaneous injection of mice with near-infrared fluorescentdye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained atthe injection site for a longer period than when soluble dye-OVA wasadministered. Coa-ASC16 alone elicited a local inflammation, but how thismaterial triggers this response has not been described yet. Although it isknown that some materials used as a platform are not immunologically inert, veryfew studies have directly focused on this topic. In this study, we explored theunderlying mechanisms concerning the interaction between Coa-ASC16 and theimmune system and we found that the whole inflammatory response elicited byCoa-ASC16 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependenton the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling werenot required for induction of this inflammatory response. Coa-ASC16 inducedlocal release of self-DNA, and in TLR9-deficient mice IL-6 production wasabsent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity whichwas affected by MyD88 and IL-6 absence. Taken together these results indicatethat Coa-ASC16 used as a vaccine platform is effective due to the combinationof the controlled release of antigen and its intrinsic pro-inflammatory activity.Understanding how Coa-ASC16 works might have significant implications for rationalvaccine design.